Synthesis of ether-linked oligoribo- and xylonucleosides from 3,5′-ether-linked pseudosaccharides

Article abstract of DOI:10.1021/jo8007429

(Chemical Equation Presented) First examples of di- and trinucleosides with ribose and xylose stereochemistry having internucleoside ether linkage were synthesized from 3,5′-ether-linked pseudosaccharides. The synthetic protocol involved removal of 1,2-isopropylidene protecting groups from the pseudosaccharides followed by acetylation and a subsequent Vorbrueggen transglycosylation with uracil and N-benzoylaminopurine. The synthetic strategy is potentially important for the development of RNA analogues with internucleoside ether linkage.

Full text of DOI:10.1021/jo8007429

SCHEME 1. General Strategy for the Conversion of
Ether-Linked Pseudosaccharides to Ether-Linked
Oligonucleosides
Synthesis of Ether-Linked Oligoribo- and
Xylonucleosides from 3,5′-Ether-Linked
Pseudosaccharides
Jhimli Sengupta and Anup Bhattacharjya*
Indian Institute of Chemical Biology, 4, Raja S. C. Mullick
Road, Kolkata 700032, India
anupbh@hotmail.com
ReceiVed April 3, 2008
1,2-isopropylidene-protected furanoside rings. The anomeric
sites of these molecules or molecules derived from them are
amenable to functionalization via deprotection and subsequent
reactions such as diol cleavage and transglycosylation. We
previously demonstrated the synthetic potential of these pseu-
dosaccharides by their conversion to novel macrooxacycles4 and
nucleosides incorporating medium-ring oxacycles.5 More im-
portantly, the structure of 1 suggests that oligopentose deriva-
tives with this general structure could be converted to oligo-
nucleosides having internucleoside ether linkage. The particular
significance of such a process lies in the future development of
hitherto unknown ether-backbone RNA analogues. Modification
of the backbone structure of DNA and RNA is a topic of
paramount interest due to their potential application in antisense
therapy.6 As a first step toward the realization of this goal, we
herein describe the synthesis of the first examples of 3,5′-ether-
linked di- and trinucleosides 2 from the corresponding pseu-
dosaccharides 1 (Scheme 1).
The general strategy for the above synthetic exercise outlined
in Scheme 1 consists of the removal of the isopropylidene
groups in 1 followed by acetylation and subsequent Vorbru¨ggen
transglycosylation7 with a suitable nucleobase (B). The outcome
would be an ether-linked oligonucleoside 2. It should be
mentioned at the outset that this strategy would furnish
nucleosides carrying a single type of base. The implementation
of the strategy is described in the following sequel.
First examples of di- and trinucleosides with ribose and
xylose stereochemistry having internucleoside ether linkage
were synthesized from 3,5′-ether-linked pseudosaccharides.
The synthetic protocol involved removal of 1,2-isopropy-
lidene protecting groups from the pseudosaccharides followed
by acetylation and a subsequent Vorbru¨ggen transglycosy-
lation with uracil and N-benzoylaminopurine. The synthetic
strategy is potentially important for the development of RNA
analogues with internucleoside ether linkage.
Ether-linked pseudosaccharides constitute a relatively little
known class of carbohydrate derivatives despite their biological
and synthetic importance.1 The primary feature of an ether-
linked pseudosaccharide is that two sugar units are combined
by a nonphosphate ether linkage. The sugar anomeric positions
remain free in these molecules, and can be used for further
structural modfication. The examples of ether-linked pseudoo-
ligosaccharides are scarce, and only a few 2,6′-, 3,6′-, and 6,6′-
ether-linked dihexoses and a 5,5′-ether-linked dipentose are
known.1–3 Recently, we reported the synthesis of the first
examples of 3,5′-ether-linked oligosaccharides from readily
available carbohydrate derivatives.4 The general structure of a
3,5′-ether-linked oligopentose is represented by 1 (Scheme 1).
A special structural feature of 1 is the presence of the
(5) Sengupta, J.; Mukhopadhyay, R.; Bhattacharjya, A. J. Org. Chem. 2007,
72, 4621.
(6) (a) Leumann, C. J. Bioorg. Med. Chem. 2002, 10, 1. (b) Rozners, E.;
Katkevica, D.; Bizdena, E.; Stro¨mberg, R. J. Am. Chem. Soc. 2003, 125, 12125,
and references cited therein. (c) Gogoi, K.; Gunjal, A. D.; Kumar, V. A. Chem.
Commun. 2006, 2373. (d) Vasseur, J-J.; Debart, F.; Sanghvi, Y. S.; Cook, P. D.
J. Am. Chem. Soc. 1992, 114, 4007. (e) Huang, J.; McElroy, E. B.; Widlanski,
T. S. J. Org. Chem. 1994, 59, 3520. (f) Musicki, B.; Widlanksi, T. S. Tetrahedron
Lett. 1991, 32, 1267. (g) McElroy, E. B.; Bandaru, R.; Huang, J. X.; Widlanski,
T. S. Bioorg. Med. Chem. Lett. 1994, 4, 1071. (h) Perrin, K. A.; Huang, J.;
McElroy, E. B.; Iams, K. P.; Widlanski, T. S. J. Am. Chem. Soc. 1994, 116,
7427. (i) Miller, P. S.; McFarland, K. B.; Jayaraman, K.; Ts’o, P. O. P.
Biochemistry 1981, 20, 1878. (j) Wozniak, L. A.; Pyzowsky, J.; Wieczorek, M.;
Stec, W. J. J. Org. Chem. 1994, 59, 5843. (k) Lesnikwosky, Z. J.; Jaworska,
M.; Stec, W. J. Nucleic Acids Res. 1990, 18, 2112. (l) Jones, R. J.; Lin, K. Y.;
Milligan, J. F.; Wadwani, S.; Matteucci, M. D. J. Org. Chem. 1993, 58, 2983.
(m) Richert, C.; Roughton, A. L.; Brenner, S. A. J. Am. Chem. Soc. 1996, 118,
4518. (n) Egholm, M.; Burchardt, O.; Nielsen, P. E.; Berg, R. H. J. Am. Chem.
Soc. 1992, 114, 1895. (o) Zhang, L.; Peritz, A.; Meggers, E. J. Am. Chem. Soc.
2005, 127, 4174.
(1) (a) Haines, A. H. Tetrahedron Lett. 2004, 45, 835. (b) Haines, A. H.
Org. Biomol. Chem. 2004, 2, 2353.
(2) (a) Whistler, R. L.; Frorein, A. J. Org. Chem. 1961, 26, 3946. (b) Hodosi,
G.; Kovac´, P. Carbohydr. Res. 1998, 308, 63. (c) Vanbaelinghem, L.; Gode´, P.;
Goethals, G.; Martin, P.; Ronco, G.; Villa, P. Carbohydr. Res. 1998, 311, 89.
(d) Takahashi, H.; Fukuda, T.; Mitsuzuka, H.; Namme, R.; Miyamoto, H.;
Ohkura, Y.; Ikegami, S. Angew. Chem., Int. Ed. 2003, 42, 5069.
(3) Biswas, G.; Sengupta, J.; Nath, M.; Bhattacharjya, A. Carbohydr. Res.
2005, 340, 567.
(7) (a) Niedballa, U.; Vorbru¨ggen, H. J. Org. Chem. 1974, 39, 3654. (b)
Niedballa, U.; Vorbruggen, H. J. Org. Chem. 1974, 39, 3660. (c) Vorbru¨ggen,
H.; Krolikewiez, K.; Bennua, B. Chem. Ber. 1981, 114, 1234. (d) Vorbru¨ggen,
H.; Ho¨fle, G. Chem. Ber. 1981, 114, 1256.
(4) Sengupta, J.; Mukhopadhyay, R.; Bhattacharjya, A.; Bhadbhade, M. M.;
Bhosekar, G. V. J. Org. Chem. 2005, 70, 8579.
6860 J. Org. Chem. 2008, 73, 6860–6863
10.1021/jo8007429 CCC: $40.75 2008 American Chemical Society
Published on Web 07/26/2008

SCHEME 2. Synthesis of Pseudotrisaccharide 10 and
Trinucleoside 12 with Ribose Stereochemistry
SCHEME 3. Synthesis of Ether-Linked Trinucleosides with
Xylose Stereochemistry
serious consequence, because the next transglycosylation step
was expected to furnish only the ꢀ nucleoside. This is why 11
was subjected to transglycosylation reaction without further
purification and characterization. Treatment of 11 with uracil
in the presence of N,O-bis(trimethylsilyl)acetamide (BSA) and
trimethylsilyl trflate (TMSOTf) led to the ether-backbone uracil
ribotrinucleoside 12 in 50% yield (Scheme 2). The structure of
12 was secured by 1H and 13C NMR and mass spectral analyses.
The introduction of three uracil moieties was evident from the
1
comparison of the H NMR integrations of the three doublets
due to uracil 5′-H’s at δ 7.50-7.67 and the OMe protons. The
ꢀ-anomeric stereochemistry of 12 and other nucleosides syn-
thesized in this work was established by the observed chemical
shift (∼δ 6 ppm) and J1,2 (1.0 to 4.8 Hz) similar to those for
ꢀ-nucleosides reported in the literature.6m,7a,b The exclusive
formation of the ꢀ-anomer was due to the anchimeric assistance
of the 2-O-acetyl group in Vorbru¨ggen type coupling.7 The
nucleoside 12 represents the first example of an oligonucleoside
containing an internucleoside ether linkage.8
The 3,5′-ether-linked pseudosaccharide 7 was synthesized
according to Scheme 2. The known4 pseudodisaccharide alde-
hyde 3 was reduced to alcohol 4 and then to mesyl derivative
5. Alkylation of 1,2:5,6-diisopropylidene-allofuranose (6) with
5 under the reported4 condition for etherification in the presence
of tetrabutylammonium bromide in aqueous NaOH led to the
pseudotrisaccharide 7 in 82% yield (Scheme 2). The structure
of 7 was consistent with the 1H and 13C NMR as well as mass
spectral data. A sequence of reactions involving removal of the
5,6-isopropylidene group giving diol 8, NaIO4-mediated vicinal
diol cleavage and reduction with NaBH4 gave alcohol 9 in 71%
overall yield from 8. Methylation of 8 led to the 5′-capped
pseudosaccharide 10 (Scheme 2), the OMe serving as a marker
in the characterization of the subsequent compounds by 1H NMR
spectroscopy. The stereochemistry of the pseudosaccharide 10
at 3-C corresponds to that found in a typical ribonucleic acid.
The next step was the application of the strategy outlined in
Scheme 1 to 10. The presence of the isopropylidene protected
furanoside ring in 10 offered a unique opportunity for introduc-
ing nucleobases at the anomeric sites, and the Vorbru¨ggen
method of transglycosylation was employed for this purpose
as described below.
The above strategy could also be applied to the synthesis of
trixylonucleosides.9 The known4 aldehyde 14 was converted to
methyl ether 16 via alcohol 15 as outlined in Scheme 3. The
application of the previously mentioned transglycosylation
method to 16 gave rise to the uracil trinucleoside 17 in 50%
yield. The corresponding N-benzoyladenine nucleoside 18 was
prepared in 20% yield by using N-benzoylaminopurine in the
presence of N-methyl-N-(trimethylsilyl)trifluoroacetamide (MST-
1
FA) and TMSOTf. The H and 13C NMR and mass spectral
data of 17 and 18 were in good agreement with the assigned
structures.
Ether-linked dinucleosides were also prepared by employing
the strategy described above. Methyl ether 19 obtained from
(8) Unlike 12, the application of the Vorbru¨ggen method using N-benzoy-
laminopurine led to a product, which was found to be extremely sensitive to
purification by column chromatography or HPLC. However, the ESI mass
spectrum of the product obtained immediately after isolation exhibited a strong
peak at m/z 1280 (M + Na) corresponding to the molecular weight of the adenine
nucleoside 13 (Scheme 2).
(9) Oligoxylonucleotides are important candidates in antisense therapy and
have been found to bind to natural nucleic acids leading to the formation of
triple helices: (a) Schoppe, A.; Hinz, H. J.; Rosenmeyer, H.; Seela, F. Eur.
J. Biochem. 1996, 239, 33. (b) Sokolova, N. I.; Dolinnaya, N. G.; Krynetskaya,
N. F.; Shabarova, Z. A. Nucleosides, Nucleotides Nucleic Acids 1990, 9, 515.
(c) Ivanov, S.; Alekseev, Y.; Bertrand, J.-R.; Malvy, C.; Gottikh, M. B. Nucleic
Acids Res. 2003, 31, 4256.
Treatment of 10 with aqueous H2SO4 followed by acetylation
gave 11 (Scheme 2), which represents a mixture of eight
diastereomers due to the presence of R and ꢀ anomers of each
of the furanose rings. This configurational scramble was of no
J. Org. Chem. Vol. 73, No. 17, 2008 6861

SCHEME 4. Synthesis of Ether-Linked Dinucleosides with
Ribose and Xylose Stereochemistry
4H), 4.08-4.28 (m, 4H), 4.33 (dd, J ) 3.9, 11.6 Hz, 1H), 4.49 (d,
J ) 10.5 Hz, 1H), 4.63 (t, J ) 3.7 Hz, 1H), 4.72 (t, J ) 3.6 Hz,
1H), 5.23 (d, J ) 10.2 Hz, 1H), 5.33 (d, J ) 17.2 Hz, 1H),
5.76-5.77 (m, 2H), 5.89-6.02 (m, 1H). A mixture of 64 (0.27 g,
1.03 mmol), 5 (1 g, 2.08 mmol), tetrabutylammonium bromide
(0.067 g, 0.20 mmol), and NaOH (0.66 g, 16.5 mmol) in water
(5.0 mL) was heated with stirring at 70 °C for 70 h. The mixture
was then extracted with CH2Cl2, and the organic layer was washed
with water and dried. Removal of solvent afforded a syrupy residue,
which was chromatographed (EtOAc-petroleum ether, 3:17) giving
7 (0.45 g, 82%) as a colorless sticky liquid: [R]25D +119.0 (c 0.44,
CHCl3); IR (neat) 1375, 1654 cm-1; MS (FAB) m/z 667 (M +
1
Na), 629 (M - CH3); H NMR δ 1.35 (s, 6H), 1.36 (s, 3H), 1.37
(s, 3H), 1.45 (s, 3H), 1.55 (s, 3H), 1.59 (s, 3H), 1.60 (s, 3H),
3.77-3.95 (m, 6H), 3.97-4.06 (m, 3H), 4.08-4.13 (m, 5H),
4.34-4.35 (m, 1H), 4.59 (t, J ) 4.0 Hz, 1H), 4.66 (t, J ) 3.9 Hz,
1H), 4.71 (t, J ) 3.7 Hz, 1H), 5.22 (d, J ) 9.6 Hz, 1H), 5.32 (d,
J ) 17.2 Hz, 1H), 5.73-5.76 (m, 3H), 5.90-6.03 (m, 1H); 13C
NMR δ 25.1 (CH3), 26.1 (CH3), 26.4 (CH3), 26.7 (CH3), 65.0 (CH2),
67.7 (CH2), 68.2 (CH2), 71.5 (CH2), 74.8 (CH), 77.0 (CH), 77.1
(CH), 77.4 (CH), 77.7 (CH), 77.8 (CH), 78.0 (CH), 78.4 (CH),
78.5 (CH), 79.3 (CH), 103.7 (CH), 103.71 (CH), 103.9 (CH), 109.5
(q), 112.6 (q), 112.64 (q), 112.7 (q), 117.6 (CH2), 134.5 (CH). Anal.
Calcd for C31H48O14, C, 57.75; H, 7.50. Found: C, 57.51; H, 7.63.
General Method of Preparation of Uracil Nucleosides. The
general method of the preparation of uracil nucleosides is illustrated
by that of 12 via the combination of method A and method B.
Method A: Deprotection of Pseudosaccharide Methyl Ethers
and Subsequent Acetylation. A stock solution was prepared by
mixing CH3CN, water, and concd H2SO4 in a volumetric ratio 18:
6:1. A mixture of 10 (0.4 g, 0.68 mmol) in this solution (15 mL)
was stirred at 25 °C for 24 h. The solution was neutralized by adding
solid CaCO3, and the mixture was filtered. The residue was washed
with acetonitrile and the combined washings were concentrated
under reduced pressure. To a solution of the resulting deprotected
compound in pyridine (10 mL) were added acetic anhydride (0.52
mL, 5.77 mmol) and a catalytic amount of DMAP at 0 °C. The
mixture was stirred at 25 °C for 4 h. Excess Ac2O was destroyed
by adding water, and the resulting AcOH was removed by
azeotropic distillation with toluene. The residue was chromato-
graphed (EtOAc-petroleum ether, 9:1) to give 11 as a syrupy liquid,
which was transglycosylated as described below.
Method B: Transglycosylation with Uracil. To a solution of
this material (0.35 g, 0.49 mmol) in CH3CN (15 mL) containing
uracil (0.33 g, 2.92 mmol) was added with stirring BSA (1.8 mL,
7.29 mmol), and the mixture was heated at reflux for 1 h. Then
TMSOTf (0.5 mL, 2.48 mmol) was added at 0 °C, and the mixture
was heated at 50 °C for 15 h. The reaction was quenched with
cold saturated NaHCO3 solution. After removal of solvent, the
residue was extracted with ethyl acetate, washed with brine, dried,
and concentrated to afford a sticky liquid, which was chromato-
graphed (CHCl3-MeOH, 24:1) to give 12 (0.3 g, 50%) as a white
solid: mp 138-140 °C; [R]25D -8.4 (c 0.21, CHCl3); IR (neat) 1380,
1695, 1738, 3209, 3509 cm-1; MS (FAB) m/z 899 (M + Na), 877
(M + H); 1H NMR δ 2.11 (s, 3H), 2.13 (s, 3H), 2.15 (s, 3H), 3.46
(s, 3H), 3.51-3.57 (m, 2H), 3.73-4.08 (m, 7H), 4.16-4.27 (m,
6H), 5.18-5.39 (m, 5H), 5.76-6.04 (m, 7H), 7.50 (d, J ) 7.7 Hz,
1H), 7.60 (d, J ) 8.0 Hz, 1H), 7.67 (d, J ) 8.2 Hz, 1H), 9.36 (bs,
1H), 9.42 (bs, 2H); 13C NMR δ 20.7 (CH3), 59.4 (CH3), 69.8 (CH2),
71.9 (CH2), 72.1 (CH2), 74.0 (CH), 75.6 (CH), 77.2 (CH), 78.0
(CH), 80.9 (CH), 81.2 (CH), 81.4 (CH), 87.6 (CH), 88.1 (CH),
90.9 (CH), 102.8 (CH), 103.0 (CH), 103.2 (CH), 117.8 (CH2), 133.7
(CH), 139.8 (CH), 140.0 (CH), 140.6 (CH), 150.4 (q), 150.6 (q),
150.7 (q), 163.5 (q), 169.9 (q), 169.94 (q), 170.2 (q); HRMS (ESI,
positive ion) calcd for C37H44N6O19Na m/z 899.2559, found
899.2498.
alcohol 4 in 88% yield by methylation was converted to the
uracil dinucleoside 20 (51%) and the protected adenine dincleo-
side 21 (21%) (Scheme 4). Similarly, the known4 pseudosac-
charide alcohol 22 afforded the uracil dinucleoside 24 (58%)
and the adenine dinucleoside 25 (31%) via the methyl-capped
pseudosaccharide 23 (Scheme 4). The sets of nucleosides 20/
21 and 24/25 have the ribose and xylose stereochemistry,
respectively.
In conclusion, the synthetic exercise described above revealed
a novel strategy for the synthesis of oligonucleosides having
internucleoside ether linkage as well as furanose rings with
varied stereochemistry. Future development in this strategy will
target the synthesis of oligonucleosides carrying different types
of bases in the same molecule by changing the precursors of
the starting pseudosaccharides. Another important modification
will involve the incorporation of a four-atom internucleoside
ether linkage, as opposed to two-atom in the present case, which
would result in closer RNA analogues consisting of an ether
backbone. The study of the complementary base pairing
interactions in these molecules will be another important topic
of the future research.10
Experimental Section
Pseudotrisaccharide 7. To a solution of the alcohol 4 (Sup-
porting Information) (0.85 g, 2.11 mmol) and triethylamine (0.59
mL) in CH2Cl2 (30 mL) was added dropwise a solution of
CH3SO2Cl (0.21 mL, 2.71 mmol) in CH2Cl2 (5.0 mL) at 0 °C, and
the mixture was stirred at 25 °C for 1 h. The mixture was poured
into crushed ice and stirred for 0.5 h. It was then extracted with
CH2Cl2, and the organic layer was washed with saturated aq
NaHCO3 solution. Removal of solvent from the organic extract gave
mesyl derivative 5 (0.93 g, 92%) as a pale yellow syrupy liquid,
1
which was used without further purification for the next step: H
NMR δ 1.36 (s, 6H), 1.57 (s, 6H), 3.05 (s, 3H), 3.80-3.96 (m,
(10) Although no detailed study has been made regarding the complementary
interaction between the uracil and adenine nucleosides, the 1H NMR spectrum
of a mixture of 17 and 25 indicated downfield shifts of 0.338-0.387 ppm for
the uracil NH protons suggesting H-bonding interaction, albeit small, between
the uracil and the adenine moieties (Supporting Information). A similar interaction
was observed in the CD spectra of 12/21 and 17/25 (Supporting Information).
General Method of Preparation of N-Benzoyladenine
Nucleosides. The general method is illustrated by the synthesis of
25 via the combination of method A and method C.
6862 J. Org. Chem. Vol. 73, No. 17, 2008

Method A: Deprotection and Subsequent Acetylation. A stock
solution was prepared by mixing CH3CN, water, and concd H2SO4
in a volumetric ratio 18:6:1. A mixture of 23 (0.11 g, 0.26 mmol)
in this solution (10 mL) was stirred at 25 °C for 24 h. The solution
was neutralized by adding solid CaCO3, and the mixture was
filtered. The residue was washed with acetonitrile, and the combined
washings were concentrated under reduced pressure. To a solution
of the resulting deprotected compound in pyridine (5 mL) were
added acetic anhydride (0.12 mL, 1.29 mmol) and a pinch of DMAP
at 0 °C. The mixture was stirred at 25 °C for 4 h. Excess Ac2O
was destroyed by addition of water, and the resulting AcOH was
removed by azeotropic distillation with toluene The residue was
chromatographed (EtOAc-petroleum ether, 3:2) to give the cor-
responding acetate as a viscous liquid, which was transglycosylated
as described below.
MS (ESI) m/z 885 (M + Na), 863 (M + H); 1H NMR (600 MHz,
CDCl3) δ 2.19 (s, 3H), 2.22 (s, 3H), 3.40 (s, 3H), 3.63-3.65 (m,
1H), 3.76-3.79 (m, 1H), 3.84 (dd, J ) 5.4, 10.2 Hz, 1H), 3.89
(dd, J ) 5.4, 12.6 Hz, 1H), 3.95 (d, J ) 4.2 Hz, 1H), 4.01 (dd, J
) 7.2, 10.8 Hz, 1H), 4.07 (dd, J ) 4.2, 12.0 Hz, 1H), 4.11-4.15
(m, 1H), 4.44-4.49 (m, 2H), 5.17 (dd, J ) 1.2, 10.8 Hz, 1H), 5.22
(dd, J ) 1.2, 16.8 Hz, 1H), 5.37 (s, 1H), 5.42 (s, 1H), 5.70-5.76
(m, 1H), 6.40-6.42 (m, 2H), 7.52-7.54 (m, 4H), 7.60-7.63 (m,
2H), 8.03 (d, J ) 7.2 Hz, 2H), 8.05 (d, J ) 7.2 Hz, 2H), 8.37 (s,
1H), 8.40 (s, 1H), 8.79 (s, 1H), 8.81 (s, 1H), 9.04 (bs, 1H), 9.08
(bs, 1H); 13C NMR δ 20.80 (CH3), 20.83 (CH3), 59.4 (CH3), 69.1
(CH2), 69.6 (CH2), 71.0 (CH2), 79.4 (CH), 80.0 (CH), 80.2 (CH),
81.8 (CH), 82.2 (CH), 87.4 (CH), 87.5 (CH), 119.0 (CH2), 123.0
(q), 127.90 (CH), 127.93 (CH), 128.9 (CH), 132.6 (CH), 132.8
(CH), 133.6 (q), 141.8 (CH), 149.4 (q), 151.7 (q), 152.7 (CH), 164.7
(q), 169.6 (q); HRMS (ESI, positive ion) calcd for C42H42N10O11Na
m/z 885.2932, found 885.2961.
Method C: Transglycosylation with N-Benzoyladenine. To a
solution of N-benzoylaminopurine (0.15 g, 0.63 mmol) in CH3CN
(10 mL) was added with stirring MSTFA (0.28 mL, 1.51 mmol),
and the mixture was stirred at 25 °C for 1 h. A solution of the
above acetate (0.1 g, 0.2 mmol) in CH3CN (5 mL) and TMSOTf
(0.05 mL, 0.24 mmol) was added to the above mixture at 0 °C,
and the mixture was heated at 80 °C for 50 h. The reaction was
quenched with cold saturated NaHCO3 solution. After removal of
solvent, the residue was extracted with ethyl acetate, and the organic
layer was washed with brine, dried, and concentrated to afford an
oily liquid, which was chromatographed (EtOAc-MeOH, 49:1) to
give 25 (0.07 g, 31%) as a sticky pale yellow material: [R]25D -45.3
Acknowledgment. A.B. thanks CSIR, India, for the award
of Emeritus Scientist Fellowship. J.S. is grateful to CSIR, India,
for Research Associateship.
Supporting Information Available: Experimental procedure,
1H and 13C NMR spectra, EIMS of 13, and CD spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(c 0.10, CHCl3); IR (neat) 1378, 1651, 1699, 1749, 3322 cm-1
;
JO8007429
J. Org. Chem. Vol. 73, No. 17, 2008 6863